Specific enrichment of antigen‐binding receptors from sensitized murine lymphocytes

Krawinkel, Ulrich; Rajewsky, Klaus

doi:10.1002/eji.1830060802

Cited by 39 publications

(18 citation statements)

References 24 publications

(7 reference statements)

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“…Initially, Binz and Wigzell (5) were the first to report the expression of Ig idiotypic determinants on alloreactive T cells. Their findings were rapidly confirmed by many workers studying other systems (6)(7)(8)(9)(10). The availability of antigens capable of eliciting antibody responses characterized by the expression of dominant crossreactive idiotypes (CRI), under the control of Ig heavychain (Igh)-linked genes, made these systems ideal for the study of the expression of Ig-like structures on T cells.…”

mentioning

confidence: 55%

“…The availability of antigens capable of eliciting antibody responses characterized by the expression of dominant crossreactive idiotypes (CRI), under the control of Ig heavychain (Igh)-linked genes, made these systems ideal for the study of the expression of Ig-like structures on T cells. Using anti-CRI reagents, idiotopes were detected on T cells specific for the azobenzenearsonate (ABA) (7), 4-hydroxy-3-nitrophenyl acetyl (8,9) or phosphorylcholine (10) determinants solely in mouse strains with the appropriate Igh genotype. It was clear, however, from numerous studies (11,12) that the idiotopes expressed on T cells, in these systems susceptible to careful immunochemical analysis, represented only a small fraction of the B-cell idiotopes.…”

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confidence: 99%

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Chronic treatment with rabbit anti-mouse mu-chain antibody alters the characteristic immunoglobulin heavy-chain restriction of murine suppressor T-cell factors.

Lowy

HayGlass

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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Prolonged treatment of mice, starting at birth, with rabbit anti-mouse jI-chain antibodies resulted in the elimination of immunoglobulin-bearing B cells in these animals. The ability of these animals to elicit antigen-specific delayed-type hypersensitivity or cytotoxic T-cell responses to azobenzenearsonate-coupled spleen cells was not impaired. The effect of anti-jA treatment on the restriction by immunoglobulin heavy-chain genes (Igh) of suppressor T cells was investigated. We found that first-order suppressor T-cell factor (TsF1) obtained from anti-IA treated animals expresses an Igh restriction pattern distinct from that observed with TsF1 from normal untreated mice. Furthermore, TsF1 prepared from anti-I treated animals did not express the major crossreactive idiotypic determinants normally present in TsF1. The significance of these findings in relation to the role of immunoglobulin on the T-cell repertoire is discussed.Since the discovery of the idiotypic determinants of immunoglobulins by Oudin and Michel (1) and independently by Kunkel et al. (2), these specific structures have been shown to play an important role in the regulation of immune responses (reviewed in ref.3). Jerne (4) was the first to perceive the enormous potential for effective regulation, inherent in the ability of the immune system to produce anti-idiotypic antibodies, and to correctly postulate the existence of autologous anti-idiotypic antibodies as autologous mirror images of the antigens that elicited the original idiotypic antibodies. The Jerne idiotypic network of immune regulation of antibody responses has been amply confirmed and documented (3). The development of anti-idiotypic antibodies reactive with specific immunoglobulins stimulated the analysis of T cells for the presence of B-cell idiotypes. Initially, Binz and Wigzell (5) were the first to report the expression of Ig idiotypic determinants on alloreactive T cells. Their findings were rapidly confirmed by many workers studying other systems (6-10). The availability of antigens capable of eliciting antibody responses characterized by the expression of dominant crossreactive idiotypes (CRI), under the control of Ig heavychain (Igh)-linked genes, made these systems ideal for the study of the expression of Ig-like structures on T cells. Using anti-CRI reagents, idiotopes were detected on T cells specific for the azobenzenearsonate (ABA) (7), 4-hydroxy-3-nitrophenyl acetyl (8, 9) or phosphorylcholine (10) determinants solely in mouse strains with the appropriate Igh genotype. It was clear, however, from numerous studies (11,12) that the idiotopes expressed on T cells, in these systems susceptible to careful immunochemical analysis, represented only a small fraction of the B-cell idiotopes. Because of the apparent Igh-linked genetic control of the expression of idiotopes on T cells, and in spite of their limited specificities, the conclusion was, nevertheless, tentatively reached by workers in many laboratories including our own, that these results indicated the contri...

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confidence: 55%

mentioning

confidence: 99%

Chronic treatment with rabbit anti-mouse mu-chain antibody alters the characteristic immunoglobulin heavy-chain restriction of murine suppressor T-cell factors.

Lowy

HayGlass

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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“…These' antibodies were iross-linked wich ECLH Immunosorbents of anti-Id antibodies and other proteins (see Sect. 2.4) were prepared as previously described [20]. The preparation of NP-and NIP-immunosorbents was carried out * We give an anti-Id antibody and its target Id the same designation.…”

Section: Strain Distribution Of Bl-8 Id and Their Association With Eamentioning

confidence: 99%

The immune response against anti‐idiotope antibodies. I. Induction of idiotope‐bearing antibodies and analysis of the idiotope repertoire

et al. 1982

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In the present analysis we dissect the idiotype repertoire, independently of hapten-binding specificity, by immunizing different strains of mice with cross-linked monoclonal anti-idiotope antibodies against antibody B1-8. B1-8 is a monoclonal antibody with specificity for the hapten (4-hydroxy-3-nitro-phenyl)acetyl (NP) and carries a germ line gene-encoded variable region. The results demonstrate that the expression of B1-8 idiotopes and their association with each other and with NP-binding specificity are strain-specific. Certain idiotopes are expressed on antibodies differing in antigen-binding specificity, whereas one of the idiotopes appears strictly associated with NP-binding antibodies. The genetic analysis provides strong evidence that the strain specificity of the idiotope repertoire is a result of V region polymorphism in the mouse.

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“…To elucidate if this initial viability decrease was due to cell damage in the filter or to disaggregation of cell clumps containing dead cells in their interior, an experiment was carried out with CHO‐3D6 cells that had been harvested and frozen during the conventional perfusion cultivation, when perfusion was carried out through the internal hollow‐fiber membranes. The enzyme DNAse I, which can be used as an additive in mammalian cell cultivations for disaggregating cell clumps (14, 15), was added to a spinner flask at a concentration of 15 mg L ‐ 1 , while another spinner flask without DNAse I was monitored as control. As shown in Figure 3, viability decreased in the DNAse I‐containing spinner flask, while it remained approximately constant in the control flask.…”

Section: Resultsmentioning

confidence: 99%

An Integrated Process for Mammalian Cell Perfusion Cultivation and Product Purification Using a Dynamic Filter

Castilho

Anspach

Deckwer

2002

Biotechnology Progress

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In the present work, a dynamic filter was employed to develop an integrated perfusion/purification process. A recombinant CHO cell line producing a human anti‐HIV IgG was employed in the experiments. In the first part of this work, the dynamic filter was fitted with conventional microfiltration membranes and tested as a new external cell retention device for perfusion cultivations. The filter was connected to a running perfusion bioreactor and operated for approximately 400 h at an average cell concentration of 10 million cells mL−1, whereby cell viability remained above 90% and no problems of sterility were experienced. In the second part of this work, the dynamic filter was employed to simultaneously carry out cell separation and product purification, using membrane adsorbers containing Protein A affinity ligands. An automated system was built, which integrated the features of an automated perfusion bioreactor and of a liquid chromatography system. The IgG was continuously adsorbed onto the affinity membranes and was periodically recovered through elution cycles. After connection of the filter, the system was operated for approximately 300 h, whereby three elution cycles were carried out. No progressive increase in transmembrane pressure was observed, indicating no membrane fouling problems, and the IgG was recovered practically free of contaminants in a 14‐fold concentrated form, indicating that the integrated, one‐step perfusion/purification process developed during this work is a promising alternative for the production of biologicals derived from mammalian cells.

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Specific enrichment of antigen‐binding receptors from sensitized murine lymphocytes

Cited by 39 publications

References 24 publications

Chronic treatment with rabbit anti-mouse mu-chain antibody alters the characteristic immunoglobulin heavy-chain restriction of murine suppressor T-cell factors.

Chronic treatment with rabbit anti-mouse mu-chain antibody alters the characteristic immunoglobulin heavy-chain restriction of murine suppressor T-cell factors.

The immune response against anti‐idiotope antibodies. I. Induction of idiotope‐bearing antibodies and analysis of the idiotope repertoire

An Integrated Process for Mammalian Cell Perfusion Cultivation and Product Purification Using a Dynamic Filter

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